Although heparin is a widely used anticoagulant, our knowledge of its clinical pharmacology is limited. This is thought to be to a large extent due to its chemical heterogeneity. Also, its clinical use continues to be assoicated with relatively high incidence of hemorrhagic complications and insufficient therapy. This project concerns itself with studies aimed at increasing our understanding in this area, in particular with respect to studies that may lead to safer and more efficacious use of this anticoagulant. This involves studies 1) to identify determinants of the anticoagulant effect of heparin, including several plasma proteins and general coagulation status, 2) to characterize the clinical pharmacokinetics of heparin, in both normal volunteers and patients, with particular respect ot its dose- and time-dependent kinetics and defining determinants thereof, 3) to evaluate the effects of heparin administration on the distribution of selected drugs, that are involved in plasma protein binding displacement interactions due to heparin-induced release of nonesterified fatty acids.